Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: MYO6 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_004999.4(MYO6):c.2836C>T (p.Arg946Cys)

CA177354

164639 (ClinVar)

Gene: MYO6
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: fe2fd572-a746-4126-b1ab-8f0f90eabde2
Approved on: 2024-12-18
Published on: 2025-03-28

HGVS expressions

NM_004999.4:c.2836C>T
NM_004999.4(MYO6):c.2836C>T (p.Arg946Cys)
NC_000006.12:g.75890234C>T
CM000668.2:g.75890234C>T
NC_000006.11:g.76599951C>T
CM000668.1:g.76599951C>T
NC_000006.10:g.76656671C>T
NG_009934.1:g.146043C>T
NG_009934.2:g.146042C>T
ENST00000369975.6:c.2836C>T
ENST00000369977.8:c.2836C>T
ENST00000369985.9:c.2836C>T
ENST00000627432.3:c.2845C>T
ENST00000664640.1:c.2836C>T
ENST00000671923.1:c.*943C>T
ENST00000672093.1:c.2836C>T
ENST00000369975.5:c.2836C>T
ENST00000369977.7:c.2836C>T
ENST00000369981.7:c.2836C>T
ENST00000369985.8:c.2836C>T
ENST00000430435.1:c.25C>T
ENST00000615563.4:c.2836C>T
ENST00000627432.2:c.2836C>T
NM_001300899.1:c.2836C>T
NM_004999.3:c.2836C>T
NM_001300899.2:c.2836C>T
NM_001368136.1:c.2836C>T
NM_001368137.1:c.2836C>T
NM_001368138.1:c.2821C>T
NM_001368865.1:c.2836C>T
NM_001368866.1:c.2836C>T
NR_160538.1:n.3161C>T
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 25
BP5 BP7 BP2 BP3 BP1 BP4 BS4 BS3 BS1 BS2 PVS1 PP4 PP1 PP2 PP3 PM6 PM2 PS2 PS4 PS3 PS1 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.2836C>T(NM_004999.4) variant in MYO6 is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 946 (p.Arg946Cys).​ The filtering allele frequency of the c.2836C>T variant in the MYO6 gene is 0.12% for South Asian chromosomes by the Genome Aggregation Database v4 (94/63976 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss variants (BA1). (ClinGen Hearing Loss VCEP specifications version 2; 12.18.2024)
Met criteria codes
BA1
The filtering allele frequency (the lower threshold of the 95% CI of 94/63976) of the c.2836C>T variant in MYO6 is 0.1229% for South Asian chromosomes by the Genome Aggregation Database v4 (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is higher than the ClinGen Hearing Loss VCEP threshold (>0.1%) for BA1, and therefore meets this criterion (BA1).
Not Met criteria codes
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
revel score must be below 0.15 to meet BP4
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The filtering allele frequency (the lower threshold of the 95% CI of 94/63976) of the c.2836C>T variant in MYO6 is 0.1229% for South Asian chromosomes by the Genome Aggregation Database v4 (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is higher than the ClinGen Hearing Loss VCEP threshold (>0.1%) for BA1, and therefore meets this criterion (BA1).
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
revel score must be below 0.15 to meet BP4
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The filtering allele frequency (the lower threshold of the 95% CI of 94/63976) of the c.2836C>T variant in MYO6 is 0.1229% for South Asian chromosomes by the Genome Aggregation Database v4 (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is higher than the ClinGen Hearing Loss VCEP threshold (>0.1%) for BA1, and therefore meets this criterion (BA1).
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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